Aza-cyano-oxabicyclo alkanes



United States Patent 3,375,249 AZA-CYANO-OXABICYCLO ALKANES Herbert E. Johnson, South Charleston, W. Va., assignor g? [anion Carbide Corporation, a corporation of New or No Drawing. Filed Aug. 23, 1963, Ser. No. 304,240 21 Claims. (Cl. 260-244) This invention relates, in general, to novel aza-cyanooxabicyclo alkanes and to a process for their preparation. In one aspect, this invention relates to a novel class of 1- aza-2-cyano-oxabicyclo alkanes. In a particular aspect, this invention relates to novel sub-classes of 1-aza-2- cyano-6,7- and S-oxabicyclo alkanes and to a process for their preparation.

It has now been found, quite unexpectedly, that a novel class of l-aza-Z-cyano-oxabicyclo alkanes can be prepared by reacting a dicyanohydrin with a primary amino alco hol, or a dialdehyde, diketone or ketoaldehyde with a primary amino alcohol in the presence of cyanide ion, e.g., as hydrogen cyanide. In the light of previous work, it was expected that the above reactions would produce high yields of dicyanopyrrolidines, dicyanohomopiperidines and dicyanopiperidines, but instead, the reaction took an unexpected course giving rise to the novel class of l-aza-Z-cyano-oxabicyclo alkanes of this invention.

The novel class of 1-aza-2-cyano-oxabicyclo alkanes of this invention can be conveniently represented by Formula I:

wherein R and R are each hydrogen or a monovalent hydrocarbon radical such as a member selected from the group consisting of alkyl, alkynyl, alkenyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalalkyl, aryl, alkylaryl, arylalkyl, and arylalkenyl groups; R and R are each hydrogen or a monovalent hydrocarbon radical such as a member selected from the group consisting of alkyl, alkynyl, alkenyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, arylalkyl, alkylaryl, and arylal-kenyl groups; n is a whole positive number or integer of from 2 to 4, inclusive; and m is a whole positive number or integer of from 2 to 6, inclusive. In the above Formula I, R through R can represent the same or dilferent groups on the same molecule. Preferably, the monovalent hydrocarbon radical contains from 1 to 25 carbonatorns.

The more preferred members of the novel class of laza-2-cyano-oxabicyclo alkanes of this invention can be conveniently represented by Formula II:

3,375,249 Patented Mar. 26, 1968 wherein R, R R R n and m are each as hereinbefore defined with reference to Formula 1. Of these more preferred compounds represented by Formula II, particularly preferred compounds are those wherein R, R R and R are either hydrogen or alkyl of from 1 to 25 carbon atoms; n is a whole positive number of from 2 to 4, inclusive; and m is a whole positive number of from 2 to 6, inclsive. The most preferred compounds represented by Formula II are those wherein R, R R and R are either hydrogen or alkyl of from 1 to 6 carbon atoms; n has a value of 3; and m is a whole positive number of from 2 to 6, inclusive, especially 2 to 3, inclusive. The most highly preferred compounds are those wherein R is hydrogen or alkyl of from 1 to 6 carbon atoms; R is hydrogen; and R and R are either hydrogen or alkyl of from 1 to 6 carbon atoms.

For convenience and clarity of expression, the novel l-aza-Z-cyano-oxabicyclo alkanes of this invention have been named as alkane derivatives, rather than as monocyanopiperidine, homopiperidine and pyrrolidine derivatives. In doing so, Chemical Abstracts nomenclature for bicyclic-heterocyclic systems has been adopted. But, the 1-aza-2-cyano-oxabicyclo alkanes of this invention also can he looked upon as monocyanopiperidine, monocyanohomopiperidine, and monocyanopyrrolidone derivatives.

Due to the outstanding and desirable physiological characteristics possessed by many of the heterocyclic nitrogen-containing compounds, the novel l-aza-2-cyano-oxabicyclo alkanes of the present invention are currently of interest as pharmaceutical intermediates. They can readily be converted at the 2-cyano position to the corresponding 2-carboxy compounds which are also useful as chemical intermediates. Moreover, the novel 1-aza-2-cyano-oxabicyclo alkanes of the present invention have additional, effective biological properties per se which render them useful in agricultural applications. They have shown biological activity toward a variety of organisms which attack plant life. In particular, they have shown activity as plant bactericides, fungicides, nematocides and herbicides.

It is accordingly an object of the present invention to provide a novel class of 1-aza-2-cyano-oxabicyclo alkanes which are suitable for use in the pharmaceutical and agricultural fields. Another object ofthis invention is to provide new compositions of matter comprising novel 1-, aza-2-cyano-oxabicyclo alkanes. A further object of the present invention is to provide a novel sub-class of -l-aZa-2- cyano-6-oxabicyclo alkanes. A still further object is to provide a novel sub-class of l-aza-2-cyano-7-oxabicyclo alkanes. Another object is to provide a novel sub-class of 1eaza-2-cyano-8-oxabicyclo alkanes. A further object of this invention is to provide a novel process for the preparation of the aforementioned novel 1-aza-2-cyano-oxaof 1-aza-2-cyano-oxabicyclo alkanes and to a process for their preparation.

In one form of the present invention, the novel class of 1-aza-2-cyano-oxabicyclo alkanes include the sub-class of 1-aza-2-cyano-7-oxabicyclo alkanes of Formula III:

Rt R1 wherein R, R R and m have the same values as hereinbefore indicated with reference to Formula II. Illustrative 1-aza-2-cyano-7-oxabicyclo alkanes include:

1-aza-2-cyano-7-oxabicyclo [4.3 .O] nonane, 1-aza-2-cyano-4-methyl-7-oxabicyclo[4.3.0]nonane, 1-aza-2-cyano-2,6-dimethyl-7-oxabicyclo[4.3.0]nonane, 1-aza-2-cyano-2,6-diethyl-7-oxabicyclo[4.3.0]nonane, 1-aZa-2-cyano-4-ethyl-7-oxabicyclo[4.3.0]nonane, 1aza-2-cyano-4-propyl-7-oxabicyclo [4.3 .0] nonane, 1-aza-2-cyano-4-isopropyl-7-oxabicyclo[4.3.0]nonane, 1aza-2-cyano-4-buty1-7-oxabicyclo[4.3.0]nonane, 1-aza-2-cyano-4-pentyl-7-oxabicycl0[4.3.0]nonane, 1-aza-2-cyano-4-hexy1-7-oxabicyclo [4.3 .0] nonane, 1-aza-2-cyano-4-heptyl-7-oxabicyclo [4.3 .0] nonane, 1-aza-2-cyano-4-octyl-7-oxabicyclo[4.3.0]nonane, 1-aza-2-cyano-3,4,5-trimethyl-7-oxabicyclo[4.3.0]nonane, 1-aza-2-cyano-3,4,5-triethyl-7-oxabicyclo[4.3.0]nonane, l-aza-2-cyano-3 ,4,-dimethyl-7-oxabicyclo [4.3 .0] nonane, 1-aza-2-cyano-3-methyl-7-oxabicyclo[4.3.0]nonane, 1-aza-2-cyano-7-oXa-8 -methylbicyclo [4.3 .0] nonane, 1-aza-2-cyano-7-oxa-8ethylbicyclo[4.3.0]nonane, 1-aza-2-cyano-7-oxa-8-isopropylbicyclo [4.3 .0] nonane, 1-aza-2-cyano-7-oxa-S-hexylbicyclo[4.3.0]nonane, l-aza-2-cyano-4,8-dimethyl-7-oxabicyclo[4.3.0]nonane, 1-aza-2-cyano-7-oxa-9,9-dimethylbicyclo[4.3.0]nonane, 1-aza-2-cyano-4,9,9-trimethyl-7-oxabicyclo[4.3.0]nonane, 1-aza-2-cyano-2,3,4,5,6-pentamethyl-7-oxabicyclo [4.3.0]nonane, 1-aza-2-cyano-2,3,4,5,6-pentaethyl-7-oxabicyclo [4.3.0]nonane, 1-aza-2-cyano-7-oxabicyclo [4.4.0] decane, 1-aza-2-cyano-4-methyl-7-oxabicyclo [4.4.0] decane, 1-aza-2-cyano-7-oxabicyclo[4.5.0]undecane, 1-aza2-cyano-7-oxabicyclo[4.6.0]dodecane, 1-aza-2-cyano-7-oxabicyclo[4.7.0]tridecane, 1-aza-2-cyano-7-oxabicyclo[4.8.0]tetradecane, 1-aza-2-cyano-7-oxabicyclo[4.9.0]pentadecane, 1-aza-2-cyano-7-oxabioyc1o[4.10.0]hexadecane,

and the like.

01: the above form represented by Formula III, those compounds most preferred are those wherein R and R are either hydrogen or alkyl of from 1 to 6 carbon atoms, R and R are each'hydrogen, or alkyl from 1 to 6, and in has a value of from 2 to 3, inclusive. When R is alkyl of from 1 to 6, and R and R are H or alkyl from 1 to 6, these compounds can be referred to as 1-aza-2- cyano-alkyl substituted-7-oxabicyclo alkanes.

In a second form of the present invention, the novel class of l-aza-Z-cyano-oxabicyclo alkanes includes as a sub-class the 1-aza-2-cyano-8-oxabicyclo alkanes of Formula IV:

wherein R, R R R and m each have the same values as hereinbefore indicated with reference to Formula II. Illustrative compounds within this form include:

1-aza-2-cyano-8-oxabicyclo [5.3.0] decane, l-aza-2-cyano-4-methyl-8-oxa-bicyclo [5 .3.0] decane, 1-aza-2-cyano-4-ethyl-8-oxabicyclo [5.3 .0] decane, l-aza-Z-cyano-4-propyl-8-oxabicyclo [5.3.0] decane, 1-aza-2-cyano-4-isopropyl-8-oxabicyclo[5 .3.0] decane, 1-aza-2-cyano-4-butyl-8-oxabicyclo [5.3 .0] decane, 1-aza-2-cyano-4-pentyl-8-oxabicyclo [5.3.0] decane, l-aza-2-cyano-4-heXy1-8-oxabicyclo [5.3 .0] decane, 1-aza-2-cyano-4-heptyl-8-oxabicyclo [5 .3 .0] decane, 1-aza-2-cyano-4-octyl-8-oxabicyclo [5.3 .0] decane, 1-aza-2-cyano-3 ,4,5 ,6-tetramethyl-8-oxabicyclo [5.3.0] decane, 1-aza-2-cy-ano-2,3,4,5,6,7-l1eXamethyl-8-oxabicyclo [5.3.0] decane, l-aza-2-cyan0-2,3,4,5,6,7-heXaethyl-8-0Xabicyc10 [5.3.0] decane, 1-aza-2-cyano-2,7-dimethyl-8-oxabicyclo[5 .3 .0] decane, 1-aza-2-cyano-2,7-diethyl 8-oXabicyclo [5.3 .0] decane, 1-aza-Z-cyano-3,4,S-triethyl-S-oxabicyelo [5.3.0] decane, l-aza-2-cyano-3 ,4-dimethyl-8-oxabicyclo [5.3 .0] decane, l-aza 2-cyano-3 -methyl-8-oxabicyclo [5 .3 .0] decane, 1-aza-2-cyano-7-methyl-8-oxabicyclo[5 .3 .0] decane, 1-aza-2-cyano-7-ethyl-8-oxabicyclo [5.3 .0] decane, 1-aza-2-cyano-7-is0propyl-8-oxabicyclo[5 .3 .0] decane, 1-aza-2cyano-7-hexyl-8-oxabicycl0 [5.3.0] decane, 1-aza-2-cyano-4,7-dimethyl-8-oxabicyclo[5 3 .0] decane, 1-aza-2-cyano-8-oxa-9,9-dimethylbicyclo [5 .3 .0] decane, 1-aza-2-cyano-4,9,9-trin1ethyl-8-oxabicyclo [5.3.0] decane, 1-aza-2-cyano-2-methyl-8-oxabicyclo [5.3.0] decane, 1-aza-2-cyano-7-methyl-8-oxabicyclo 5 .3 .0] decane, 1-a'za-2-cyan0-7-ethyl-8-oxabicyclo [5.3.0] decane, 1-aza-2-cyano-8-oxabicyclo [5 .4.0] undecane, 1-aza-2-cyano-4-methyl-8-oxabicyclo [5.4.0] undecane, 1-aza-2-cyano-8-oxabicyclo [5.5.0] dodecane, 1-aza-2-cyano-S-oxabicyclo [5.6.0] tridecane, 1-aza-2-cyano-8-oxabicyclo [5.7.0] tetradecane, 1-aza-2-cyano-8-oxabicyelo [5.8 .0] pentadecane,

and the like.

Of the above form represented by Formula IV, those compounds most preferred are those wherein R and R are either hydrogen or alkyl of from 1 to 6 carbon atoms, R and R are each hydrogen, or alkyl and m has a value of from 2 to 3, inclusive.

A third form of the present invention is directed to a novel class of 1-aza-2-cyano-oxabicyclo alkanes comprising the sub-class of 1-aza-2-cyano--oxabieyclo alkanes of Formula V:

wherein R, R R R and m each have the same values as hereinbefore indicated with reference to Formula II. Illustrative compounds within this form include, among others:

1-aza-2-cyano-6-oxabicyclo [3 .3 .0] octane, 1-aza-2-cyano-4-methyl-6-oxabieyc1o[ 3 .3.0] octane, 1-aza-2-cyano-4-ethyl-6-oxabicyclo [3.3.0] octane, 1-aza-2-cyano-4-propyl-fi-oxabicyclo 3 .3.0] octane, 1-aza-2-cyan0-4-isopropyl-6-oxabicyclo 3.3 .0] octane,

l-aza-2-cyano-4-buty1-fi-oxabicyclo[ 3 .3 .0] octane, 1-aza-2-cyano-4-pentyl-6-oxabicyclo 3. 3 .0] octane, 1-aza-2-cyano-4-hexy1-6-oxabicyclo [3.3.0] octane, 1-aza-2-cyano-4-heptyl-6-oxabicyclo 3.3.0] octane, 1-aZa-2-cyano-4-octyl-6-oxabicyclo[3 .3 .0] octane, 1-aza-2-cyano-3,4,5-trimethyl-6-oxabicyclo[3 .3 .0] octane, 1-aza-2-cyano-3,4,fitriethyl-G-oxabicyclo[3.3 .0] octane, l-aza-2-cyano-3,4-dimethyl-G-oxabicyclo [3 .3 .0] octane, l-aza-2-cyano-3 -methyl- 6-oxabicyclo [3.3.0] octane, l-aza-2-cyano-6-oxa-8-methylbicyclo [3 .3 .0] octane, 1-aza-2-cyano-6-oxa-8-ethylbicyclo [3 .3 .0] octane, l-aza2-cyano-6-oxa-8-isopropylbicyclo [3.3.0] octane, l-aza-2-cyano-6-oxa-8-hexylbicyclo [3 .3 .0]octane, 1-aza-2-cyano-4,8-dimethyl-6-oxabicyclo [3 .3 .0] octane, 1-aza-2-cyano-6-oxa-7,7-dimethylbicyclo[3 .3 .0] octane, 1-aza-2-cyano-4,7,7-trimethyl-6-oxabicyclo[ 3 .3.0] octane, 1-aza-2-cyano-2,5-dimethyl-6-oxabicyclo [3.3.0] octane, 1-aza-2-cyan0-2,5-diethyl-6-oxabicyclo [3 .3 .0] octane, 1-aza-2-cyano-2-methyl-6-oxabicyclo [3 .3 .0] octane, 1-aza-Z-cyano-'6-oxabicyclo 3 .4.0] nonane, 1-aza-2-cyano-4-methyl-6-oxabicyclo [3 .4.0] nonane, 1-aza-2-cyano-6-oxabicyclo [3 .5 .0] decane, l-aza-2-cyano-6-oxabicyclo [3 .6.0] undecane, l-aza-2-cyano-6-oxabicyclo [3 .7.0] dodecane, 1-aza-2-cyano-6-oxabicyclo [3.8.0] tridecane, l-aza-2-cyano- 6-oxabicyc1o[3 .9.0] tetradecane,

and the like.

Of the above form represented by Formula V, those compounds most preferred are those wherein R and R are either hydrogen or alkyl of from 1 to 6 carbon atoms, R and R each hydrogen, or alkyl and m has a value of from 2 to 3, inclusive.

In accordance with the process of this invention, the novel l-aza-2-cyano-oxabicyclo alkanes herein represented by Formula I, are produced in relatively high yields from readily available starting materials. The process comprises either the cyclization of a dicyanohydrin (A) with a primary amino alcohol (B), as indicated by reaction scheme (S), or the cyclization of a dialdehyde, diketone or ketoa-ldehyde with a primary amino alcohol in the presence of cyanide ion, e.g., as hydrogen cyanide.

wherein R, R R R n and m each have the same values as previously indicated with reference to Formula I.

The process can be more specifically illustrated by reaction scheme (S') wherein glutaraldehyde dicyanohywherein m is a positive whole number from 2 to 6, inclusrve.

In the above reaction schemes (S) and (5), best results are achieved with about one equivalent of the dicyanohydrin (A) or (A) in an aqueous reaction medium which is treated with a slight excess of one equivalent of the primary amino alcohol (B) or (B'). The reaction mixture is allowed to stir at a temperature of from about 25 to about 50 C., and then extracted with a suitable organic solvent, e.g., ether, to remove the desired l-aza-Z-cyano-oxabicyclo alkane. Distillation of the organic solvent extracts, e.g., ether extracts, generally affords about 40-98 percent yields of the 1-aza-2-cyanooxabicyclo alkanes of this invention. Alternatively, when the dialdehyde, diketone or ketoaldehyde is reacted with the primary amino alcohol in the presence of cyanide ion, e.g., as hydrogen cyanide, at least one equivalent of hydrogen cyanide must be used for best results.

The dicyanohydrin starting materials suitable for use in the present invention encompasses the succinaldehyde, glutaraldehyde, and adipaldehyde d-icyanohydrins and theircorresponding substituted derivatives as defined by R and R herein with reference to the formulae.

Suitable dicyanohydrin starting materials which can be utilized in the preparation of the 1 aza 2 cyano 7 oxabicyclo alkanes of the first form of this invention include the glutaraldehyde dicyanohydrins. Illustrative compounds used in the preparation of the first formv include: glutaraldehyde dicyanohydrin, 3 met-hylglutaraldehyde dicyanohydrin, 3 t butylglutaraldehyde dicyanohydrin, 3 octadecylgl-utaraldehyde dicyanohydrin, 3- allylglutaraldehyde dicyanohydrin, 3 pentenylglutaraldehyde dicyanohydrin, 3 cyclohexylglutaraldehyde dicyanohydrin, 3 cycloheptylglutaraldehyde dicyanohydrin, 3 (4 cyclohexenyl)glutaraldehyde dicyanohydrin, 3 (-cyclohexylpropyl)glutaraldehyde dicyanohydrin, 3 benzylglutaraldehyde, dicyanohydrin, 3 (2 methylbenzyl)glutaraldehyde dicyanohydrin, 3 (p isopropylbenzyl)glutaraldehyde dicyanohydrin, 3 (bet-a styryl)- glutaraldehyde dicyanohydrin, 2,4 dimethylglutaraldedicyanohydrin, 2 methyl 4 ethyl glutaraldehyde dicyanohydrin, 2,3,4 trimethylglutaraldehyde dicyanohydrin, 2,4 dimethyl 3 propylglutaraldehyde dicyanohydrin, and the like.

For the preparation of the novel 1 aza 2 cy-ano 8- oxabicyclo alkanes of the second embodiment of the present invention the following dicyanohydrin starting materials can be employed: adipaldehyde dicyanohydrin, 3- methyladipaldehyde dicyanohydrin, 3,4 dimethyladipaldehyde dicyanohydrin, 2,3,4,5 tetramethyladipaldehyde dicyanohydrin, 3 propyladipaldehyde dicyanohydrin, 2,4,5 trimethyl 3 propyladipaldehyde dicyanohydrin, 3 allyladipaldehyde dicyanohydrin, 3 octade-cyladipaldehyde dicyanohydrin, 3 pentenyladipaldehyde dicyanohydrin, 3 cyclohexyladipaldehyde dicyanohydrin, 3 cycloheptyladipaldehyde dicyanohydrin, 3,4 (4 cyclohexenyl)adipaldehyde dicyanohydrin, 3 (3 cyclohexylpropyl)adipaldehyde dicyanohydrin, 3 benzyladipaldehyde dicyanohydrin, 3 (beta-styryl)adipaldehyde dicy- .anohydrin, 2 methyl 4 benzyladipaldehyde dicyanohydrin, 2 methyl 4 pentenyladipaldehyde dicyanohydrin, and the like.

Suitable dicyanohydrins which can be used as the starting materials for the novel 1 aza 2 cyano 6 oxabicyclo alkanes of the third form of the instant invention include: succinaldehyde dicyanohydrin, 2 methylsuccinaldehyde dicyanohydrin, 3 methylsuccinaldehyde dicyanohydrin, 2,3 dimethyls-uccin-aldehyde dicyanohydrin, 2 methyl 3 ethylsuccinaldehyde dicyanohydrin, 2 octadecylsuccinaldehyde dicyanohydrin, 3 allylsuccinaldehyde dicyanohydrin, 2 pentenylsuccinaldehyde dicyanohydrin, 3 cyclohexylsuccinaldehyde dicyanohydrin, 2 benzylsuccinaldehyde dicyanohydrin, 3 (2 methylbenzyl)succinaldehyde dicyanohydrin, and the like.

Preparation of the dicyanohydrin starting materials can be elfected from readily available and inexpensive chemicals. For instance, they can be conveniently prepared in relatively high yields according to known methods by the action of hydrogen cyanide on -a dialdehyde.

As noted hereinabove, diketones and ketoaldehydes are used to prepare the compounds of this invention. Illustrative diketones used are: 2,4 pentanedione, 2,4 hexanedione, 2,4 heptanedione, methyl 2,4 hexanedione, 2,4 octanedione, 2,5 hexanedione, 2,5 octanedione, 2,5 decanedione; and illustrative ketoaldehydes are: 2 butanone, 2 pentanone, 2 hexanone, 2 heptanone, and the like.

Suitably primary amino alcohol compounds which can be utilized in the preparation of the novel compounds of this invention include, among others, the aliphatic, cycloaliphatic and arylaliphatic primary amino alcohols. Particularly suitable primary amino alcohols are the alkanolamines having one amino and one hydroxy group, and containing from 2 to 6 carbon atoms.

Typical primary amino alcohols suitable for use can be conveniently illustrated by such compounds as: aminoethanol, 2 amino 1 ethanol, 3 amino 1 propanol, 3 amino 2 propanol, 2 amino 1 propanol, 4 amino l butanol, 3 amino 1 b-utanol, 5 amino 1 pentanol, 6 amino 1 hexanol, 7 amino 1 -heptnol, 8 amino 1 -octanol, 9 amino l nonanol, l0 amino 1 decanol, 11 amino 1 undecanol, 12 amino 1 dodecanol, 2 amino 1 cyclopentanol, 2 amino 1 cyclohexanol, p-amino-phenylcarbinol, and the like.

Inasmuch as most of the dicyanohydrins, diketones or ketoaldehydes and primary amino alcohols suitable for use in the process of this invention have a relatively high degree of water solubility, an aqueous reaction medium is preferred, especially about a 25 percent solution of the dicyanohydrin, diketone or ketoaldehyde in water. In such instances, the reaction product, 1 azo 2 cyanooxabicyclo alkane, precipitates from the aqueous solution and can be readily collected by filtration or other known separation means. In those instances where the dicyanohydrin, diketone or ketoaldehyde and primary amino alcohol are sparingly soluble in water, an inert, normallyliquid, organic solvent is employed to effect solution. Ethyl alcohol, tetrahydrofuran, dioxane, chloroform and the like, are all suitable for use as the solvents. The optimum ratio of solvent to water necessary to effect solution of the components will largely be dependent upon the particular choice of primary aminoalcohol and dicyanohydrin, diketone or ketoaldehyde, as well as other considerations. This can be determined by routine experimentation. In other cases, the reaction product, monocyanoheterocyclic bicyclo compound, can be diluted with water,

extracted with a solvent such as chloroform and distilled. The distillate contains the desired reaction product. In general, the amount of reagent employed is not critical, at least one equivalent of dicyanohydrin, diketone or ketoaldehyde, to at least one equivalent of primary aminoalcohol is used. A suitable amount can range from about 1 to about 5 for the dicyanohydrin, diketone or ketoaldehyde and from about 1 to about 5 for the primary amino alcohol.

Reaction conditions suitable for effecting cyclization of the aforementioned dicyan-ohydrin starting materials, as well as diketones and ketoaldehydes, in general require temperatures within the range of from about 0 C. to about the reflux temperature of the solvent employed, i.e., up to 100 C., and higher. 'In order to avoid undesired side reactions and to provide a suitable reaction rate,

temperatures in the range of from about 10 C. to about 70 C. are preferred. However, temperatures above and below the aforesaid range can also be employed.

Reaction times of from 15 minutes to 24 hours, or more, or less, are thoroughly practicable. Shorter or longer periods can also be feasibly employed depending upon the temperature, the higher temperatures usually permitting the use of shorter reaction times.

Pressure is in no Wise critical and the reaction will proceed satisfactorily at atmospheric, subatmospheric, or superatmospheric pressures.

The novel 1-aza-2-cyano-oxabicyclo alkanes provided by the present invention can be used to prepare heterocyclic monocarboxylic acid derivatives of the aforementioned novel compounds. By the instant process, monocarboxylic acid derivatives can be prepared easily and from inexpensive and readily available starting materials. The process comprises forming a mixture, in an inert, normally-liquid solvent, of the corresponding monocyano compound prepared by the instant process, and a suitable acid, such as sulfuric acid, heating the mixture to a temperature of from about 10 C. to about the reflux temperature of the solvent, i.e., 100 C., cooling, and thereafter adding a sufficient quantity of a base, such as ammonium hydroxide, until the monocarboxylic acid precipitated from the mixture. In practice, ammonium hydroxide was added until the pH of the solution was approximately between 5-8. Suitable acids which can be employed include: sulfuric, hydrochloride, phosphoric, nitric and the like. While ammonium hydroxide has been effectively utilized to adjust the pH of the solution, other bases such as sodium hydroxide, potassium hydroxide, and the like, can also be employed. The m-onocarboxylic acids prepared from the monocyano-compounds herein, i.e., 1-aza-2-cyano-oxabicyclo alkanes, are also useful as chemical intermediates.

The following examples are illustrative of the compounds and process of the present invention.

Example I.1-aza-2-cyano-7-0xabicyclo [4.4.0] decane To a solution of 40 g. (0.25 mol) of glutaraldehyde dicyanohydrin in 150 ml. of water, was added 20 g. (0.27 mol) of 3-amino-1-propanol. The resulting mixture was held at a temperature of about 45 until the initial heat of reaction subsided and then the mixture was stirred at about 25 for approximately 20 hours (overnight). The clear reaction mixture was diluted with 500 ml. of water and extracted three times with chloroform to isolate the desired product. Distillation of the extracts, after adding 5 drops of percent phosphoric acid, afforded 28 g. of colorless distillate of 1-aza-2-cyano-7-oxabicyclo[4.4.0] decane, B.P. 104-1 10 C. (1.5 mm.). Redistillation provided an analytical Sample of 1-aza-2-cyano-7-oxabicyclo- [4.4.0]decane, B.P. -96 C. (1.0 mm), n 1.4892.

Analysis.Calc. fOr-C H N O: C, 65.03; H, 8.49; N, 16.85. Found: C, 65.13; H, 8.55; N, 16.67.

The l-aza-Z-cyano-oxabicyclo alkanes tabulated in the following table were prepared in a manner similar to that of Example I.

What is claimed is: 1. A l-aza-Z-cyano-oxabicyclo alkane of the formula:

TAB LE,l-A ZA-2-O YANO-OXABICYCLOALKANES In a manner similar to the preparation of Example I, 1 aza 2 cyano-7-oxabicyclo[4.3.0]nonane is prepared from glutaraldehyde dicyanohydrin and Z-amino-l-etha- Although the invention has been illustrated by the preceding examples, the invention is not to be construed nol; 1 aza 2-cyano-7-0xa-S-methylbicyclo[4.3.0]nonane is prepared from glutaraldehyde dicyanobydrin and 2- amino-l-methylethanol, and the like.

as limited to the materials employed therein, but rather, 70 the invention encompasses the broad class of 1-aza-2- cyano-oxabicyclo alkanes as hereinbefore disclosed. Various modifications and embodiments of this invention can be made without departing from the spirit and scope thereof.

2. A l-aza-2-cyano-7-oxabicyclo alkane of the formula:

wherein R is selected from the group consisting of hydrogen and alkyl of 1 to 6 carbon atoms and m is an integer of from 2 to 6, inclusive.

3. A l-aza-Z cyano alkyl substituted- 7 oxabicyclo alkane.

4. l-aza-2cyano-7-oxabicyclo[4.3.0]nonane.

5. l-aza 2-cyano-4-methyl-7-oxabicyclo [4.3 .0] nonane.

6. 1-aza-2-cyano-8-methyl-7-oxabicyclo[4.3.0]nonane.

7. 1 aza 2 cyano-4,8-dimethyl-7-oxabicyclo[4.3.0]

nonane.

8. 1 aza 2 cyano 7-oxa-9,9-dimethylbicyclo[4.3.0]

nonane.

9. l aza 2-cyano-4,9,9-trimethyl-7-oxabicyclo [4.3.0]

nonane.

10. 1-aza-2-cyano-7--oxabicyclo[4.4.0]decane.

11. 1 aza 2 cyano 4 methyl-7-oxabicyclo[4.4.0] decane.

12. A process for the preparation of a l-aza-Z-cyanooxabicyclo alkane of the formula:

inclusive; and m is an integer from 2 to 6, inclusive,

which comprises reacting a member selected from the group consisting of a dicyanohydrin, diketone and ketoaldehyde with a primary amino alcohol.

dim'ethyl-7 -oxabicyclo[4.3.0]nonane which comprises 13. A process for the prepartion of a 1-aza-2-cyano-7- oxabicyclo alkane of the formula:

wherein R is selected from the group consisting of hydrogen and alkyl of 1 to 6 carbon atoms and m is an integer of from 2 to 6, inclusive, which comprises reacting a .glutaraldehyde dicyanohydrin with an alkanolamine.

14. A process for the preparation of 1-aZa-2-cyano-7- oxabicyclo[4.3.0] nonane which comprises forming a mixture, in water, of glutaraldehyde dicyanohydrin and 2- amino-l-ethanol.

15. A process for the preparation of l-aza-2-cyano-4- methyl-7-oxabicyclo[4.3.0]nonane which comprises forming .a mixture, in water, of 3-methylglutaraldehyde dicyanohydrin and Z-amino-l-etnauol.

- 16. A process for the preparation of 1-aza-2-cyano-7- oxaf-8-methylbicyclo[4.3.0]nonane which comprises forming-a mixture, in water, of glutaraldehy-de dicyanohydrin and l-amino-Z-propanol.

17. A process for the prepartion of 1-aza-2-cyano-4,8-

forming a mixture, in water, of S-methylglutaraldehyde dicyanohydrin and l-amino-Z-propanol.

18. A process for the preparation of 1-aza-2cyano- 7-oxa-9, 9-dimethy1bicyclo[4.3.0]nonane which comprises forming a mixture, in water, of glutaraldehyde dicyanohydri'n and Z-amino-methyl-l-propanol.

19. A process for the prepartion of 1-aza-2-cyano-4,9,9- trimethyl 7 oxabicyclo[4.3.0]nonane which comprises forming a mixture, in water, of 3-methylglutaraldehyde and Z-amino-methyl-l-propanol.

20. A process for the preparation of 1-aZa-2-cyano-7- mixture, in water, of glutaraldehyde dicyanohydrin and B-amino-l-propanol.

21. A process for the preparation of 1-aza-2-cyano-4- methyl-7-oxabicyclo[4.4.0]decane which comprises forming a mixture, in water, of 3-methy1glutaraldehyde and 3-am'ino-1-propanol.

No references cited.

IOHND. RANDOLPH, Primary Examiner.

WALTER A. MODANCE, Examiner. ROBERT T. BOND, Assistant Examiner. 

1. A 1-AZA-2-CYANO-OXABICYCLO ALKANE OF THE FORMULA:
 12. A PROCESS FOR THE PREPARATION OF A 1-AZA-2-CYANOOXABICYCLO ALKANE OF THE FORMULA: 